Areplivir tablets p / o 200mg, No. 40

Treating a new coronavirus infection (COVID-19).

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

Applied in a hospital setting.

Inside, 30 minutes before meals.

For patients weighing less than 75 kg: 1600 mg 2 times / day on the 1st day, then 600 mg 2 times / day from 2 to 10 days.

For patients weighing 75 kg or more: 1800 mg 2 times / day on the 1st day, then 800 mg 2 times / day from 2 to 10 days.

The total duration of the course of treatment is 10 days or until confirmation of the elimination of the virus, if it occurs earlier (two consecutive negative PCR test results obtained with an interval of at least 24 hours).

Film-coated tablets of light yellow color, round, biconvex; in cross section, the core is white or almost white.

1 tab.

favipiravir 200 mg

Excipients: povidone K30, colloidal silicon dioxide, low-substituted hyprolose, microcrystalline cellulose type 101, crospovidone, stearic acid.

Composition of the film casing: ready-made film coating OpadrayЃ 03F220114 yellow [hypromellose. titanium dioxide, macrogol 4000 (polyethylene glycol 4000), dye iron oxide yellow E172].

Hypersensitivity to favipiravir; severe hepatic impairment (class C according to the Child-Pugh classification); severe renal failure and end-stage renal failure (GFR <30 ml / min); pregnancy, planning pregnancy, breastfeeding period; children under 18 years of age.

Carefully

Patients with a history of gout and hyperuricemia (possibly an increase in uric acid levels and exacerbation of symptoms), elderly patients, patients with moderate hepatic impairment (GFR <60 ml / min and? 30 ml / min).

Clinical and pharmacological group: Antiviral drug

Pharmaco-therapeutic group: Antiviral agent

pharmachologic effect

This medicinal product is registered under the registration procedure for medicinal products intended for use in conditions of threat of occurrence, occurrence and elimination of emergencies. The instruction was prepared based on the limited amount of clinical data on the use of the drug and will be supplemented as new data becomes available. The use of the drug is possible only in inpatient medical care.

Antiviral drug.

Antiviral activity in vitro

Favipiravir has antiviral activity against laboratory strains of influenza A and B viruses (EC50 0.014-0.55 ?g / ml).

For strains of influenza A and B viruses resistant to adamantane (amantadine and rimantadine), oseltamivir or zanamivir, the EC50 is 0.03-0.94 ?g / ml and 0.09-0.83 ?g / ml, respectively. For influenza A virus strains (including strains resistant to adamantane, oseltamivir and zanamivir) such as type A swine influenza and type A avian influenza, including highly pathogenic strains (including H5N1 and H7N9), the EC50 is 0.06-3.53 ?g / ml.

Favipiravir inhibits the SARS-CoV-2 virus, which causes the new coronavirus infection (COVID-19). The EC50 in Vero E6 cells is 61.88 ?mol, which corresponds to 9.72 ?g / ml.

Mechanism of action

Favipiravir is metabolized in cells to favipiravir ribosyl triphosphate (Favipiravir RTF) and selectively inhibits RNA-dependent RNA polymerase involved in influenza virus replication. RTF favipiravir (1000 ?mol / L) showed no inhibitory effect on ? of human DNA, but showed an inhibitory effect in the range from 9.1 to 13.5% on ? and in the range from 11.7 to 41.2% for? human DNA. The inhibitory concentration (IC50) of RTF favipiravir for human RNA polymerase II was 905 ?mol / L.

Resistance

After 30 passages in the presence of favipiravir, no changes were observed in the susceptibility of influenza type A viruses to favipiravir, and no resistant strains were observed either. In the clinical studies carried out, the appearance of influenza viruses resistant to favipiravir was not detected.

Pharmacokinetics

Favipiravir is readily absorbed from the gastrointestinal tract. Tmax 1.5 hours. Plasma protein binding is about 54%. Favipiravir is mainly metabolized by aldehyde oxidase and partially metabolized to the hydroxylated form by xanthine oxidase. RTF of favipiravir is metabolized in cells. Among other metabolites, in addition to hydroxylate, glucuronate conjugate was also recorded in human blood plasma and urine. It is excreted mainly by the kidneys in the form of an active metabolite of hydroxylate, a small amount - unchanged. T1 / 2 about 5 hours.

In patients with mild and moderate hepatic impairment (class A and B according to the Child-Pugh classification), an increase in Cmax and AUC was observed by 1.5 times and 1.8 times, respectively, compared with healthy volunteers. In patients with severe hepatic impairment (class C according to the Child-Pugh classification), Cmax and AUC increased 2.1 times and 6.3 times, respectively.

In patients with moderate renal insufficiency (GFR <60 ml / min and ?30 ml / min), the residual concentration of favipiravir (Ctrough) increased 1.5-fold compared with patients without renal impairment. In patients with severe and end-stage renal failure (GFR <30 ml / min), favipiravir has not been studied.

Side effect

On the part of the blood and lymphatic system: often - neutropenia, leukopenia; rarely - leukocytosis, monocytosis, reticulocytopenia.

From the side of metabolism: often - hyperuricemia, hypertriglyceridemia; infrequently - glucosuria; rarely hypokalemia.

From the immune system: infrequently - rash; rarely - eczema, itching.

From the respiratory system: rarely - bronchial asthma, sore throat, rhinitis, nasopharyngitis.

From the digestive system: often - diarrhea; infrequently - nausea, vomiting, abdominal pain; rarely - abdominal discomfort, duodenal ulcer, bloody stools, gastritis.

From the liver and biliary tract: often - increased activity of ALT, AST, GGT; rarely - an increase in the activity of alkaline phosphatase, an increase in the concentration of bilirubin in the blood.

Others: rarely - abnormal behavior, increased CPK activity, hematuria, laryngeal polyp, hyperpigmentation, impaired taste sensitivity, hematoma, blurred vision, eye pain, vertigo, supraventricular extrasystoles, chest pain.

Application during pregnancy and lactation

In preclinical studies of favipiravir at doses similar to clinical ones, or at lower doses, early embryo death and teratogenicity were observed.

Favipiravir is contraindicated in pregnant women, as well as in men and women during pregnancy planning.

If it is necessary to use favipiravir in women capable of childbearing, as well as in postmenopausal women for less than 2 years, it is necessary to confirm a negative pregnancy test result before starting treatment. A repeat pregnancy test should be done after you stop taking favipiravir.

Women who are fertile and men who are fertile should be fully aware of the risks associated with taking favipiravir.

When distributed in the human body, favipiravir enters the semen.

It is necessary to use the most effective methods of contraception (condom with spermicide) during and after treatment with favipiravir: within 1 month for women and within 3 months for men.

Additionally, it is necessary to instruct male patients not to have sex with pregnant women.

If you suspect a possible pregnancy, you should immediately stop taking the drug and consult your doctor.

If it is necessary to use it during lactation, it is necessary to stop breastfeeding during treatment with favipiravir and within 7 days after its termination. the main metabolite of favipiravir is excreted in breast milk.

Application for violations of liver function

Contraindications: severe hepatic impairment (class C according to the Child-Pugh classification).

With caution: patients with moderate hepatic impairment (GFR <60 ml / min and? 30 ml / min).

Application for impaired renal function

Contraindications: severe renal failure and end-stage renal failure (GFR <30 ml / min).

Application in children

Contraindicated for use in children and adolescents under the age of 18 years.

Use in elderly patients

Use with caution in elderly patients.

special instructions

Application is possible only in a hospital environment.

With the development of side effects, it is necessary to report this in the prescribed manner for the implementation of pharmacovigilance measures.

Before taking favipiravir, it is necessary to provide written information to the patient about the effectiveness of the drug and the risks associated with its use (including the risk of affecting the embryo and fetus) and obtain written consent to use the drug.

Influence on the ability to drive vehicles and mechanisms

Care should be taken when driving and operating machinery.

Drug interactions

Favipiravir is not metabolized by isoenzymes of the cytochrome P450 system, mainly metabolized by aldehyde oxidase and partially metabolized by xanthine oxidase. Inhibits aldehyde oxidase and CYP2C8 isoenzyme, but does not induce cytochrome P450 isoenzymes.

With simultaneous use with pyrazinamide, hyperuricemia is observed due to an additional increase in the reabsorption of uric acid in the renal tubules.

With simultaneous use with repaglinide, it is possible to increase the concentration of repaglinide in the blood and develop undesirable reactions due to the action of repaglinide.

With simultaneous use with famciclovir, sulindac, their effectiveness may decrease due to inhibition of aldehyde oxidase by favipiravir, which can lead to a decrease in the concentration of active forms of these substances in the blood.